Systemic Capillary Leak Syndrome (SCLS) is a disorder of unknown cause characterized by episodes of life-threatening drop in blood pressure and leakage of fluids into tissues. The outcome from an episode of SCLS may be mild and resolve on its own, or may be severe and result in death. Although SCLS likely involves abnormalities in the cells lining blood vessels, the specific cause(s) of this disorder are not known.

The treatment of choice for an acute SCLS episode is intravenous fluids and drugs such as norepinephrine (adrenaline), which are given to keep blood pressure at a level that will maintain vital organ function. This may be followed by a course of intravenous steroids and IVIG. Currently, there is no cure, but IVIG has been effective in diminishing the frequency and/or intensity of SCLS episodes when given regularly, as long-term effective preventive therapy for many patients who experience recurrent episodes of SCLS.

This protocol is focused on understanding what causes SCLS with the hope that research findings will lead to the design of safe and more effective treatments.

Patients between 16 and older who have been diagnosed with SCLS. Patients who have been diagnosed with SCLS and are between the ages of 7 and 16 may participate off-site, by sending specimens to the NIH. Patients 16 and older who have been diagnosed with SCLS and cannot travel to the NIH may also participate off-site.

Patients must have a documented history of at least one episode of SCLS with all three of the following documented on at least one occasion: low blood volume, low blood pressure without cause, and evidence of protein leakage during the episode. A letter of a referral from a treating physician is also required.

Design:

Patients seen on site will be evaluated at the National Institutes of Health (NIH) for approximately 4 to 5 days on an inpatient basis, and will undergo the following procedures:

Medical history and physical examination.

Blood samples for evaluation and research purposes, as well as possible genetic testing.

Apheresis procedure, if needed, to obtain a larger volume of blood cells for research.

Bone marrow biopsy, if medically indicated.

Other medically indicated tests, such as skin tests to check for possible allergic reactions.

Patients who have a capillary leak episode while at NIH will be treated with the standard of care for treating SCLS.

Patients will be discharged from the protocol 1 year after the NIH visit.

Patients participating off-site will be asked to collect and send specimens (such as blood) to the NIH for research purposes and evaluation.

Unaffected Biological relatives of SCLS patients and Unrelated Normal Volunteers may also enroll on the study. Relatives and Normal Volunteers may be asked to provide research samples for the study, such as skin biopsy and research blood specimens.

Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment:

210

Study Start Date:

July 2009

Detailed Description:

The systemic capillary leak syndrome (SCLS, Clarkson syndrome) is an exceedingly rare disorder of unknown cause characterized by chronic edema or acute transient, severe episodes of hypotension, hypovolemia, and oliguria. Severe edema results from leakage of fluid and macromolecules (200-900 kDa) into tissues. Acute SCLS episodes carry a high morbidity and mortality (25-30%). Only 150 cases have been reported worldwide since 1960, although the disease may be underdiagnosed due to the nonspecific nature of the presenting signs and symptoms and the considerable overlap with other shock syndromes including sepsis, anaphylaxis, and angioedema. Approximately 85% of such individuals have a monoclonal gammopathy of unknown significance (MGUS), but the relationship of this finding to disease pathogenesis is unclear. This protocol will focus on the pathogenesis of SCLS. Subjects with documented episodes of capillary leak will be evaluated in order to correlate both clinical and laboratory features that are typical of SCLS. The goal is to identify biological factors and/or genetic and molecular events that may predispose to SCLS episodes. We plan to enroll up to 210 subjects, family members and healthy volunteers in this study. We anticipate that our findings may be a first step toward the development of new targeted therapies.

Eligibility

Ages Eligible for Study:

16 Years to 80 Years (Child, Adult, Senior)

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

Yes

Criteria

PARTICIPANT INCLUSION CRITERIA:

Subjects with SCLS UNDER16 years of age are only eligible for components of this protocol that can occur Off Site and can be sent in to the NIH.

All subjects must be at least 16 years old to participate in any other aspects of this protocol.

Diagnosis or suspected diagnosis of Systemic Capillary Leak Syndrome by a physician or documented history of capillary leak as characterized by one or more of the following:

Clinical evidence of fluid extravasation (e.g. edema) and/or laboratory evidence of protein extravasation such as serum hypoalbuminemia (less than 3.5 g/dL) either chronically or during an acute hypotensive episode.

Letter of referral, with copies of pertinent medical history and laboratory studies, from prospective study subject s referring physician. Patients may self-refer, but a letter of referral from primary physician is still required.

Ability to give informed consent, or parent or guardian able to give informed consent. A Medical/Legal Guardian or Legally Authorized Representative may give consent for an incapacitated adult SCLS subject.

Willing to donate blood for sample storage to be used for future research.

Willing to donate blood for sample storage to be used for future research.

Subjects must be at least 16 years old.

Able to give informed consent.

PARTICIPANT EXCLUSION CRITERIA:

Presence of conditions which in the judgment of the investigator or the referring physician may put the subject at undue risk for travel (including frequent episodes of severe capillary leak, symptoms not preventable by pre-medication, acute infection, severe thrombocytopenia [minimum platelet count of 30,000/microL], or significant cardiovascular disease)

Any condition that in the view of the principal investigator would make the subject unsuitable for enrollment in this study

There is an identified cause for your hypotensive episodes and/or tissue swelling.

Subjects under the age of 16 are only eligible for components of this protocol that can occur Off Site and can be mailed in to the NIH, such as collection of research samples. Subjects under the age of 16 are otherwise excluded from other components of this protocol.

Presence of conditions which in the judgment of the investigator may put the subject at undue risk

Any condition that in the view of the principal investigator would make the subject unsuitable for enrollment in this study

PARTICIPATION OF CHILDREN:

No relatives or healthy volunteers below the age of 16 will be enrolled. However, children (age <16 years) with SCLS may participate in components of this protocol that can occur Off Site and can be mailed in to the NIH, such as collecting research specimens through the local care provider and sending the samples to the NIH. Due to the life-threatening nature of SCLS episodes, intensive care management may be required. The NIH clinical center does not have pediatric intensive care unit facilities. In addition, the prevalence of SCLS in children is extremely low.

PARTICIPATION OF ADULT SUBJECTS UNABLE TO CONSENT:

Adult subjects unable to provide consent during an acute episode of SCLS may be included in this study. Specimens from an acute phase of an SCLS episode are time-sensitive, and may yield critical information regarding potential causative factors or acute cellular abnormalities that correlate with clinical features of SCLS. Due to the life-threatening nature of SCLS episodes, a subject may suddenly require intensive care management at the subject s local institution, rendering the subject unable to provide his/her own consent. While incapacitated, a Medical/Legal Guardian or Legally Authorized Representative (LAR) may provide Off Site consent for the collection of time-sensitive, critical specimens. An NIAID staff member who is able to obtain consent for this protocol may obtain consent from the Medical/Legal Guardian or LAR. Although there may be no direct benefit to the subject, research blood specimens may be obtained with minimal risk, and tissue samples will only be obtained as described in section 4.1.6. Once the acute phase resolves, and the subject is able to give his/her own consent, a previously incapacitated adult may be re-consented.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00936325